This Project examines the cellular neuropathology and pathogenesis of four HIV-related neurological disorders: demyelination of peripheral nerve; predominantly sensory neuropathy; vacuolar myelopathy; and HIV encephalopathy. Cases of these disorders chosen for detailed study will be identified clinically or by systematic screening of autopsies. In all of these disorders, the first goal is detailed definition of the cellular neuropathology. Throughout this Project, we will use neurobiological approaches to investigate the behavior of myelin-forming cells and neurons. In the demyelinating neuropathies, we will examine Schwann cell mRNA levels for myelin proteins and ask how they may be altered during demyelination and remyelination. In particular, we will ask if Schwann cell response are different, comparing the demyelinating neuropathies seen in early autopsies of AIDS patients. We will ask if the sensory neuropathy is a dying-back disorder of primary sensory neurons associates with rostral gracile tract degeneration and how sensory neurons respond in terms of perikaryal functions. In vacuolar myelopathy, we will examine different stages of lesions and ask if oligodendrocyte synthesis of myelin proteins, as estimated by mRNA content, is decreased on increased. In HIV encephalopathy, we will determine whether neurons are lost in regions associated with other types of dementia, if there are alterations in specific neurotransmitter system, if the diffuse myelin pallor reflects demyelination or alterations in myelin maintenance, and if oligodendrocyte synthetic functions are altered. In all, are will investigate the possible role of HIV infection of neural cells.